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T 细胞特异性长非编码 RNA 在携带 HLA 风险/非风险等位基因的系统性红斑狼疮患者中的表达模式。

Expression patterns of T cells-specific long noncoding RNAs in systemic lupus erythematosus patients carrying HLA risk/nonrisk alleles.

机构信息

School of Medicine, Department of Internal Diseases Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.

School of Medicine, Department of Immunology, Hamadan University of Medical Sciences, Hamadan, Iran.

出版信息

Lupus. 2023 Sep;32(10):1188-1198. doi: 10.1177/09612033231196626. Epub 2023 Aug 23.

DOI:10.1177/09612033231196626
PMID:37610356
Abstract

BACKGROUND

Long noncoding RNAs (LncRNAs) play key roles in the regulation of gene expression and subsequently in the pathogenesis of several autoimmune diseases. This study aimed to explore the peripheral expression levels of T-cells-specific LncRNAs and transcription factors in systemic lupus erythematosus (SLE) patients carrying either human leukocyte antigens (HLA) risk or non-risk alleles.

METHODS

Genotypes of and loci for 106 SLE patients were determined by PCR-SSP. In the next step, patients were stratified based on the presence of and/or allele groups (HLA risk alleles positive or HLA-R) or carrying other allele groups (HLA-R). Then, transcript levels of LncRNAs ( and ) and mRNAs for transcription factors ( and ) were measured using qRT-PCR and compared between two subgroups of patients.

RESULTS

Totally, 47 cases were classified as HLA-R and 59 cases as HLA-R patients. The HLA-R patients showed decreased transcript levels of ( = .001) and elevated expression of ( = .06) and mRNA ( = .03) compared to the HLA-R group. We observed significantly lower expression of ( < .0001) and ( = .001) and higher expression of ( = .009) and ( = .02) in positive versus -negative patients. Likewise, decreased transcript levels of ( = .02) and ( = .003) were observed in positive versus -negative patients. ROC curve analysis revealed the potential of and as biomarkers in SLE disease based on the carriage of HLA risk alleles.

CONCLUSIONS

Our results indicate that the contribution of multiple T cell subsets in SLE disease progression as judged by expression analysis of LncRNAs and transcription factors can be inspired by the inheritance of HLA risk/nonrisk alleles is SLE patients.

摘要

背景

长链非编码 RNA(lncRNAs)在基因表达的调控中发挥关键作用,进而在几种自身免疫性疾病的发病机制中发挥关键作用。本研究旨在探讨携带人类白细胞抗原(HLA)风险或非风险等位基因的系统性红斑狼疮(SLE)患者 T 细胞特异性 lncRNAs 和转录因子的外周表达水平。

方法

通过 PCR-SSP 确定 106 例 SLE 患者的 和 基因座基因型。下一步,根据是否存在 和/或 等位基因组(HLA 风险等位基因阳性或 HLA-R)或携带其他 等位基因组(HLA-R)将患者分层。然后,使用 qRT-PCR 测量 lncRNAs(和 )和转录因子(和 )的 mRNA 转录水平,并在两组患者之间进行比较。

结果

总共 47 例患者被归类为 HLA-R,59 例患者为 HLA-R。与 HLA-R 组相比,HLA-R 患者的 (=.001)转录水平降低, (=.06)和 (=.03)mRNA 表达升高。与 阴性患者相比,我们观察到 (<.0001)和 (=.001)的表达显著降低, (=.009)和 (=.02)的表达升高。同样,在 阳性与 阴性患者中,观察到 (=.02)和 (=.003)的转录水平降低。ROC 曲线分析显示,基于 HLA 风险/非风险等位基因的遗传, 和 作为 SLE 疾病生物标志物具有潜力。

结论

我们的结果表明,通过 lncRNAs 和转录因子表达分析,可以判断 HLA 风险/非风险等位基因遗传对 SLE 患者疾病进展的影响,T 细胞亚群在 SLE 疾病中的作用。

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